title: Impaired functions of macrophage from cystic fibrosis patients: CD11b, TLR-5 decrease and sCD14, inflammatory cytokines increase.
abstract: BACKGROUND
  Early in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated in literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant role in the initiating stages of this disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction may be the first step in cascade of events leading to chronic inflammation/infection in CF. Moreover, reports have suggested that CFTR contribute to altered inflammatory response in CF by modification of normal macrophage functions.
  
  
  OBJECTIVE
  In order to highlight possible intrinsic macrophage defects due to impaired CFTR, we have studied inflammatory cytokines secretions, recognition of pathogens and phagocytosis in peripheral blood monocyte-derived macrophages from stable adult CF patients and healthy subjects (non-CF).
  
  
  RESULTS
  In CF macrophage supernatants, concentrations of sCD14, IL-1β, IL-6, TNF-α and IL-10 were strongly raised. Furthermore expression of CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR inhibition in non-CF macrophages also led to alterations of phagocytosis function as well as CD11b expression.
  
  
  CONCLUSIONS
  Altogether, these findings demonstrate excessive inflammation in CF macrophages, characterized by overproduction of sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5, and impaired phagocytosis. This leads to altered clearance of pathogens and non-resolution of infection by CF macrophages, thereby inducing an exaggerated pro-inflammatory response.
authors.affiliation: Université de Rennes 1, Structure Fédérative de Recherche Biosit, F-35043 Rennes, France ; Institut de Recherche Santé Environnement & Travail (IRSET), Institut National de la Santé et de la Recherche Médicale (INSERM), U1085, team 'Stress Membrane and Signaling', F-35043 Rennes, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Simonin-Le Jeune
authors.forename: André
authors.initials: A
authors.lastname: Le Jeune
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.forename: Chantal
authors.initials: C
authors.lastname: Belleguic
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Roux
authors.forename: Marie
authors.initials: M
authors.lastname: Jaguin
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Dimanche-Boitre
authors.forename: Valérie
authors.initials: V
authors.lastname: Lecureur
authors.forename: Caroline
authors.initials: C
authors.lastname: Leclercq
authors.forename: Benoît
authors.initials: B
authors.lastname: Desrues
authors.forename: Graziella
authors.initials: G
authors.lastname: Brinchault
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gangneux
authors.forename: Corinne
authors.initials: C
authors.lastname: Martin-Chouly
mesh_terms: D000328:Adult; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000276:immunology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005602:France; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000502:physiology; D018709:Statistics, Nonparametric; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D019005:Cystic Fibrosis Transmembrane Conductance Regulator